Researchers demystify a fountain of youth in the adult brain

Duke University Medical Center researchers have found that a "fountain of youth" that sustains the production of new neurons in the brains of rodents is also believed to be present in the human brain. The existence of a vital support system of cells around stem cells in the brain explains why stem cells by themselves can't generate neurons in a lab dish, a major roadblock in using these stem cells for injury repair.

"We believe these findings will have important implications for human therapy," said Chay Kuo, M.D., Ph.D., George Brumley Jr. assistant professor of Cell Biology, Pediatrics and Neurobiology, and senior author of the study.

The study is the cover story in the July issue of Neuron, published online July 14.

The scientists found that neighboring "epithelial-like" ependymal cells  not stem cells themselves  maintain a special structure that keeps neural stem cells "neurogenic," able to make new neurons.

Currently, when neural stem cells are harvested for growth in culture, however, the ependymal cells are not removed along with them, and this can be a problem.

"Neural stem cells in a lab dish don't continue to make neurons as they do inside the brain," Kuo said. "Instead, they often produce astrocytes, a cell type that may not be helpful to re-implant into a brain." He said that uncontrolled astrocyte growth can lead to brain tumors.

In a series of experiments, the researchers found that the generation of new neurons depended on what he calls the "ugly sibling" of the stem cells, the ependymal cell that has long, moving, hair-like cilia that cover its surface. Kuo decided to study these cells because the lateral ventricles in the brain, where adult neural stem cells reside, are also the last area of a developing brain that grows ependymal cells.

"The common radial glial progenitors in the developing nervous system prior to birth give rise to both the ependymal cells and the adult stem cells," Kuo said. "So it made sense to study these niche cells as well as the stem cells."

"There is this fountain of youth inside the adult brain that actively makes new neurons," Kuo said. "Yet we don't know how this fountain is constructed or maintained."

Kuo and his colleagues found that the Foxj1 transcription factor, a class of master proteins that turn other genes on and/or off, is critical to instruct ependymal cells to change shape and assemble into pinwheel-like architecture surrounding stem cells. He said the lateral membranes of mature ependymal cells are shaped like machine cogs or fingers that lace together.

The researchers determined that the structural protein Ankyrin 3 was turned on by Foxj1 in these ependymal cells to provide structural support for the delicate neural stem cells. Signals generated by this structural support will probably be important for instructing introduced neural stem cells to make neurons in therapeutic settings, he said.

Kuo said he would not have examined the role of ependymal cell Foxj1 in relation to neural stem cells if not for his Cell Biology Chair, Brigid Hogan, Ph.D., whose lab next door is a world leader in understanding adult lung and airway stem cell function. Likewise, Kuo said pioneering work on ankyrins by Duke Cell Biology and Howard Hughes Medical Institute Investigator Vann Bennett, M.D., Ph.D., a co-author on the paper, paved the way for study of these proteins in the neural stem cell environment.

Future studies will look closely at the details of the niche environment to learn more. "Understanding the environmental control of neuron production in the adult brain will be crucial for future therapeutic strategies using human stem cells to replace neurons," Kuo said.

Related Stories

Researchers at the Yerkes National Primate Research Center, Emory University, have discovered dental pulp stem cells can stimulate growth and generation of several types of neural cells. Findings from this study, available ...

UCSF scientists have determined that adult stem cells in a specific region of the mouse brain have a built-in mechanism that allows the cells to participate in the repair and remodeling of damaged tissue in the region.

In a development that could potentially benefit victims of degenerative neurological diseases, researchers have succeeded in stimulating the growth of neural stem cells in the adult brain. Such cells could then be directed ...

Working with embryonic mouse brains, a team of Johns Hopkins scientists seems to have discovered an almost-too-easy way to distinguish between “true” neural stem cells and similar, but less potent versions. Their finding, ...

Studies indicate that the majority of people with mood and anxiety disorders who receive the most commonly prescribed class of antidepressant medications, Selective Serotonin Reuptake Inhibitors or SSRI's, are not helped ...

Scientists from the Florida campus of The Scripps Research Institute have discovered a mechanism that causes long-term memory loss due to age in Drosophila, the common fruit fly, a widely recognized substitute for human memory ...

Like musical sounds, different states of mind are defined by distinct, characteristic waveforms, recognizable frequencies and rhythms in the electrical field of the brain. When the brain is alert and performing ...

Highly anxious people have more trouble deciding how best to handle life's uncertainties. They may even catastrophize, interpreting, say, a lovers' tiff as a doomed relationship or a workplace change as a ...